BACKGROUND: CKD-602, a topoisomerase I inhibitor, has antitumor activity in a broad spectrum of tumor types. STEALTH liposomal CKD-602 (S-CKD602) prolongs circulation of CKD-602 in plasma, increases drug exposure in tumors and improves efficacy compared with free drug. MATERIALS AND METHODS: Different dosing regimens of S-CKD602, free CKD-602 and topotecan were compared for antitumor activity in female athymic nude mice bearing human A375 melanoma, ES-2 ovarian, H82 SCLC or HT-29 colon tumor xenografts. RESULTS: S-CKD602 was more efficacious than free drug in all tumor types studied. The therapeutic index (TI) of S-CKD602 was estimated to be approximately 6-fold greater than that of free CKD-602 in ES-2 and approximately 3-fold greater in H82 tumors. TI of S-CKD602 was approximately 2-fold greater than that of free CKD-602 and approximately 5-fold greater than that of topotecan in A375, and > or = 3-fold greater in HT-29 tumors. In A375 tumors, once-weekly dosing of S-CKD602 was superior to once every 2 weeks or twice weekly schedules. CONCLUSION: The therapeutic index of S-CKD602 was greater than that of free CKD-602 and topotecan in several human tumor types.
BACKGROUND:CKD-602, a topoisomerase I inhibitor, has antitumor activity in a broad spectrum of tumor types. STEALTH liposomal CKD-602 (S-CKD602) prolongs circulation of CKD-602 in plasma, increases drug exposure in tumors and improves efficacy compared with free drug. MATERIALS AND METHODS: Different dosing regimens of S-CKD602, free CKD-602 and topotecan were compared for antitumor activity in female athymic nude mice bearing human A375 melanoma, ES-2 ovarian, H82 SCLC or HT-29 colon tumor xenografts. RESULTS: S-CKD602 was more efficacious than free drug in all tumor types studied. The therapeutic index (TI) of S-CKD602 was estimated to be approximately 6-fold greater than that of free CKD-602 in ES-2 and approximately 3-fold greater in H82 tumors. TI of S-CKD602 was approximately 2-fold greater than that of free CKD-602 and approximately 5-fold greater than that of topotecan in A375, and > or = 3-fold greater in HT-29 tumors. In A375 tumors, once-weekly dosing of S-CKD602 was superior to once every 2 weeks or twice weekly schedules. CONCLUSION: The therapeutic index of S-CKD602 was greater than that of free CKD-602 and topotecan in several humantumor types.
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Authors: Huali Wu; Ramesh K Ramanathan; Beth A Zamboni; Sandra Strychor; Suresh Ramalingam; Robert P Edwards; David M Friedland; Ronald G Stoller; Chandra P Belani; Lauren J Maruca; Yung-Jue Bang; William C Zamboni Journal: Int J Nanomedicine Date: 2012-10-19
Authors: Thomas D Pfister; Melinda Hollingshead; Robert J Kinders; Yiping Zhang; Yvonne A Evrard; Jiuping Ji; Sonny A Khin; Suzanne Borgel; Howard Stotler; John Carter; Raymond Divelbiss; Shivaani Kummar; Yves Pommier; Ralph E Parchment; Joseph E Tomaszewski; James H Doroshow Journal: PLoS One Date: 2012-12-28 Impact factor: 3.240
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